Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients
Bromocriptine mesylate (BRC), a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS) Here we report a first in human trial in ALS. A multicenter, Riluzole add-on, randomiz...
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| description | Bromocriptine mesylate (BRC), a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS) Here we report a first in human trial in ALS.
A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial.
The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7). The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1st endpoint) and upon completion or discontinuation of the study (2nd endpoint) of the dosing.
Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1st and 2nd endpoint analysis. In the 1st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%), eating and drinking (P = 2.2%), ALSFRS-R total (P = 17.6%), grip strength (P = 19.8%) compared to the placebo group. In the 2nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%), ALSAQ40-communication (P = 11.9%), eating and drinking (P = 13.6%), and neck forward-bent test (P = 15.4%) of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence.
BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment.
UMIN Clinical Trials UMIN000008527. |
| doi_str_mv | 10.1371/journal.pone.0149509 |
| format | Article |
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A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial.
The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7). The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1st endpoint) and upon completion or discontinuation of the study (2nd endpoint) of the dosing.
Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1st and 2nd endpoint analysis. In the 1st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%), eating and drinking (P = 2.2%), ALSFRS-R total (P = 17.6%), grip strength (P = 19.8%) compared to the placebo group. In the 2nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%), ALSAQ40-communication (P = 11.9%), eating and drinking (P = 13.6%), and neck forward-bent test (P = 15.4%) of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence.
BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment.
UMIN Clinical Trials UMIN000008527.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0149509</identifier><identifier>PMID: 26910108</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Amyotrophic lateral sclerosis ; Amyotrophic Lateral Sclerosis - drug therapy ; Animal models ; Apoptosis ; Biology and Life Sciences ; Bromocriptine ; Bromocriptine - adverse effects ; Bromocriptine - therapeutic use ; Care and treatment ; Clinical trials ; Combined treatment ; Consortia ; Development and progression ; Diagnosis ; Dopamine ; Dopamine D2 receptors ; Dosage ; Double-Blind Method ; Double-blind studies ; Family medical history ; Female ; Grip strength ; Hospitals ; Humans ; Inflammation ; Lactose ; Leukocyte Count ; Male ; Medical research ; Medicine ; Medicine and Health Sciences ; Middle Aged ; Neck ; Neurology ; Neuroprotection ; Oxidative stress ; Patients ; Physical Sciences ; Randomization ; Research and Analysis Methods ; Riluzole ; Riluzole - therapeutic use ; Risk factors ; Rodents ; Statistical analysis ; Treatment Outcome</subject><ispartof>PloS one, 2016-02, Vol.11 (2), p.e0149509</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Nagata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Nagata et al 2016 Nagata et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-8ffb789e19ecd9f4d6099275f6ee783d85763f8ddbf79b2b72e566a38f73a24b3</citedby><cites>FETCH-LOGICAL-c758t-8ffb789e19ecd9f4d6099275f6ee783d85763f8ddbf79b2b72e566a38f73a24b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765990/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765990/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26910108$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nagata, Eiichiro</creatorcontrib><creatorcontrib>Ogino, Mieko</creatorcontrib><creatorcontrib>Iwamoto, Kounosuke</creatorcontrib><creatorcontrib>Kitagawa, Yasuhisa</creatorcontrib><creatorcontrib>Iwasaki, Yasuo</creatorcontrib><creatorcontrib>Yoshii, Fumihito</creatorcontrib><creatorcontrib>Ikeda, Joh-E</creatorcontrib><creatorcontrib>ALS Consortium Investigators</creatorcontrib><title>Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Bromocriptine mesylate (BRC), a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS) Here we report a first in human trial in ALS.
A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial.
The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7). The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1st endpoint) and upon completion or discontinuation of the study (2nd endpoint) of the dosing.
Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1st and 2nd endpoint analysis. In the 1st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%), eating and drinking (P = 2.2%), ALSFRS-R total (P = 17.6%), grip strength (P = 19.8%) compared to the placebo group. In the 2nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%), ALSAQ40-communication (P = 11.9%), eating and drinking (P = 13.6%), and neck forward-bent test (P = 15.4%) of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence.
BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment.
UMIN Clinical Trials UMIN000008527.</description><subject>Aged</subject><subject>Amyotrophic lateral sclerosis</subject><subject>Amyotrophic Lateral Sclerosis - drug therapy</subject><subject>Animal models</subject><subject>Apoptosis</subject><subject>Biology and Life Sciences</subject><subject>Bromocriptine</subject><subject>Bromocriptine - adverse effects</subject><subject>Bromocriptine - therapeutic use</subject><subject>Care and treatment</subject><subject>Clinical trials</subject><subject>Combined treatment</subject><subject>Consortia</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Dopamine</subject><subject>Dopamine D2 receptors</subject><subject>Dosage</subject><subject>Double-Blind Method</subject><subject>Double-blind studies</subject><subject>Family medical history</subject><subject>Female</subject><subject>Grip strength</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Lactose</subject><subject>Leukocyte Count</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Neck</subject><subject>Neurology</subject><subject>Neuroprotection</subject><subject>Oxidative stress</subject><subject>Patients</subject><subject>Physical Sciences</subject><subject>Randomization</subject><subject>Research and Analysis Methods</subject><subject>Riluzole</subject><subject>Riluzole - 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drug therapy</topic><topic>Animal models</topic><topic>Apoptosis</topic><topic>Biology and Life Sciences</topic><topic>Bromocriptine</topic><topic>Bromocriptine - adverse effects</topic><topic>Bromocriptine - therapeutic use</topic><topic>Care and treatment</topic><topic>Clinical trials</topic><topic>Combined treatment</topic><topic>Consortia</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Dopamine</topic><topic>Dopamine D2 receptors</topic><topic>Dosage</topic><topic>Double-Blind Method</topic><topic>Double-blind studies</topic><topic>Family medical history</topic><topic>Female</topic><topic>Grip strength</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Lactose</topic><topic>Leukocyte Count</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Middle Aged</topic><topic>Neck</topic><topic>Neurology</topic><topic>Neuroprotection</topic><topic>Oxidative stress</topic><topic>Patients</topic><topic>Physical Sciences</topic><topic>Randomization</topic><topic>Research and Analysis Methods</topic><topic>Riluzole</topic><topic>Riluzole - therapeutic use</topic><topic>Risk factors</topic><topic>Rodents</topic><topic>Statistical analysis</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nagata, Eiichiro</creatorcontrib><creatorcontrib>Ogino, Mieko</creatorcontrib><creatorcontrib>Iwamoto, Kounosuke</creatorcontrib><creatorcontrib>Kitagawa, Yasuhisa</creatorcontrib><creatorcontrib>Iwasaki, Yasuo</creatorcontrib><creatorcontrib>Yoshii, Fumihito</creatorcontrib><creatorcontrib>Ikeda, Joh-E</creatorcontrib><creatorcontrib>ALS Consortium Investigators</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nagata, Eiichiro</au><au>Ogino, Mieko</au><au>Iwamoto, Kounosuke</au><au>Kitagawa, Yasuhisa</au><au>Iwasaki, Yasuo</au><au>Yoshii, Fumihito</au><au>Ikeda, Joh-E</au><aucorp>ALS Consortium Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-02-24</date><risdate>2016</risdate><volume>11</volume><issue>2</issue><spage>e0149509</spage><pages>e0149509-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Bromocriptine mesylate (BRC), a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS) Here we report a first in human trial in ALS.
A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial.
The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7). The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1st endpoint) and upon completion or discontinuation of the study (2nd endpoint) of the dosing.
Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1st and 2nd endpoint analysis. In the 1st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%), eating and drinking (P = 2.2%), ALSFRS-R total (P = 17.6%), grip strength (P = 19.8%) compared to the placebo group. In the 2nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%), ALSAQ40-communication (P = 11.9%), eating and drinking (P = 13.6%), and neck forward-bent test (P = 15.4%) of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence.
BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment.
UMIN Clinical Trials UMIN000008527.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26910108</pmid><doi>10.1371/journal.pone.0149509</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-02, Vol.11 (2), p.e0149509 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1950591841 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Aged Amyotrophic lateral sclerosis Amyotrophic Lateral Sclerosis - drug therapy Animal models Apoptosis Biology and Life Sciences Bromocriptine Bromocriptine - adverse effects Bromocriptine - therapeutic use Care and treatment Clinical trials Combined treatment Consortia Development and progression Diagnosis Dopamine Dopamine D2 receptors Dosage Double-Blind Method Double-blind studies Family medical history Female Grip strength Hospitals Humans Inflammation Lactose Leukocyte Count Male Medical research Medicine Medicine and Health Sciences Middle Aged Neck Neurology Neuroprotection Oxidative stress Patients Physical Sciences Randomization Research and Analysis Methods Riluzole Riluzole - therapeutic use Risk factors Rodents Statistical analysis Treatment Outcome |
| title | Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients |
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